The overall objectives of the proposed work are to elucidate mechanisms operative in the control of parathyroid hormone biosynthesis, secretion and metabolism, and factors which influence the metabolism of vitamin D. The work in progress is primarily concerned with the control of parathyroid hormone secretion and metabolism. The possible role of a calcium binding protein present in parathyroid tissue in the regulation of parathyroid hormone production is being investigated. Specifically, the effects of vitamin D status on the concentration of calcium binding protein in the parathyroid glands, and on PTH secretory rates are being studied in the dog. The effects of vitamin D therapy on PTH secretion is being studied in the human as well. The effects of magnesium on PTH secretion are being studied in vivo and in vitro. The in vitro studies are designed to determine if magnesium deficiency results in impaired production of c-AMP which in turn leads to impaired PTH secretion. The metabolism of PTH is being studied in the human in vivo. We are attempting to determine where the peripheral metabolism of PTH takes place, and the nature of the PTH fragments which are formed at the various sites of metabolism. The metabolism of PTH by isolated liver membranes is being studied in vitro. PTH fragments which are formed by liver membranes from intact PTH are being assessed for their immunological characteristics and biological activity.